Biosynthetic intermediates of the tetradehydro cyclic dipeptide albonoursin produced by Streptomyces albulus KO-23

The cell-free extract of an albonoursin-producing strain Streptomyces albul us KO-23 catalyzes the conversion of cyclo(L-Leu-L-Phe) (1) to albonoursin (2). At the early stage of this conversion, two compounds were newly formed prior to albonoursin synthesis in the reaction mixture. These compounds we re isolated and identified as (Z)-3-benzylidene-6-isobutyl-2,5-piperazinedi one (4) and (Z)-3-benzyl-6-isobutylidene-2,5-piperazinedione (3). The cell- free extract also catalyzed the conversion of compound 3 or 4 to albonoursi n. From these results, albonoursin was found to be biosynthesized via these compounds from cyclo(L-Leu-L-Phe). These didehydro diketopiperazines exhib ited no inhibitory activity toward the first cleavage of sea urchin embryo in contrast to the higher cytotoxicity for albonoursin, indicating that deh ydrogenation at alpha,beta -positions of both amino acid residues in diketo piperazines is required for cytotoxicity.